AB1443 TRIGGERING IGA VASCULITIS BY FOOD ALLERGEN EXPOSURE, VITAMIN D DEFICIENCY, AND IL-33-ACTIVATED TYPE 2 IMMUNE RESPONSES
Authors: X. MA, J. Wang, H. Jiang, Y. Shan
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Immunoglobulin A vasculitis (IgAV) is one of the most common types of systemic vasculitis in children and usually involves the skin, gastrointestinal tract, kidneys, and articulation[1]. The trigger of IgAV is unclear. Study elucidated that higher serum IgE levels and vitamin D deficiency existed in IgAV commonly[2, 3], while it is worth noting that T helper (Th) 2 cells increase in IgAV and are closely correlated with aberrant production of antibodies and the development of vessel vasculitis[4]. Moreover, serum IL-33 can activate many immune cell types involved in type 2 immune responses and allergic inflammatory reactions, are elevated in IgAV patients and positively correlated with the overall clinical score[5, 6]. This study aimed to further analyze their mutual relationship and reveal the mechanism underlying IgAV development. <h3>Objectives</h3> We investigated the levels of antigen-specific antibodies, 25-hydroxyvitamin D [25(OH)D<sub>3</sub>], and IL-33 and the phenotypes of Th cells in the peripheral blood of IgAV patients at the early stage of disease onset. We also analyzed the correlation between each index and clinical characteristics. <h3>Methods</h3> Aeroallergen-specific IgE and food-specific IgE were detected by western blotting. Serum 25(OH)D<sub>3</sub> and total IgE levels were determined by electrochemiluminescence immunoassay. Serum IL-33 and sST2 levels were detected by enzyme-linked immunoassays. Serum IL-2, IL-4, IL-6 and IL-10 were detected using a cytometric bead array. Frequencies of T helper cell subsets were detected by flow cytometry. <h3>Results</h3> About half of the patients had abnormal allergic indicators and positive results in the allergen-specific IgE assay. Up to 98.25% of the patients had decreased serum 25(OH)D<sub>3</sub> levels, which were inversely correlated with an abnormal increase in IgE. Th2 cells were elevated and negatively correlated with the level of serum 25(OH)D<sub>3</sub>. IL-33, a critical cytokine for the differentiation of Th2 cells, was also increased and negatively correlated with serum 25(OH)D<sub>3</sub> levels. <h3>Conclusion</h3> Food allergen exposure and 25(OH)D<sub>3</sub> deficiency may trigger IgAV. 25(OH)D<sub>3</sub> deficiency induces the activation of type 2 immune responses and a pathological increase in IgE by promoting the secretion of IL-33, which may be the underlying mechanism of IgAV pathogenesis. Monitoring vitamin D levels and administering vitamin D supplementation might play significant roles in preventing and treating IgAV. <h3>References</h3> [1] Sharma PP, Seshagiri DV, Nagappa M, <i>et al</i>. Role of altered IL-33/ST2 immune axis in the immunobiology of Guillain-Barre syndrome. Eur J Neurol. 2022, 29:2074-83. [2] Luca CM, Laicini EA, Fossali EF. Eosinophil cationic protein in Henoch-Schonlein purpura. World J Pediatr. 2014, 10:90-1. [3] Zhu L, Zhang C, Xiang R, <i>et al</i>. Correlations of Leukotriene B4 and 25-Hydroxyvitamin D3 Levels with Disease Severity in Children with Henoch-Schonlein Purpura. Clin Lab. 2022, 68. [4] Li YY, Li CR, Wang GB, <i>et al</i>. Investigation of the change in CD4(+) T cell subset in children with Henoch-Schonlein purpura. Rheumatol Int. 2012, 32:3785-92. [5] Cayrol C, Girard JP: Interleukin-33 (IL-33): A nuclear cytokine from the IL-1 family. Immunol Rev. 2018, 281:154-68. [6] Chen T, Jia RZ, Guo ZP, <i>et al</i>. Elevated serum interleukin-33 levels in patients with Henoch-Schonlein purpura. Arch Dermatol Res. 2013, 305:173-7. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.